LIVIVO - Search results -

Search results

Result 1 - 10 of total 11

Search options

Article: Resolving the Dynamic Motions of SARS-CoV-2 nsp7 and nsp8 Proteins Using Structural Proteomics.

Courouble, Valentine V / Dey, Sanjay Kumar / Yadav, Ruchi / Timm, Jennifer / Harrison, Jerry Joe E K / Ruiz, Francesc X / Arnold, Eddy / Griffin, Patrick R

bioRxiv : the preprint server for biology

2021

Abstract: Coronavirus (CoV) non-structural proteins (nsps) assemble to form the replication-transcription complex (RTC) responsible for viral RNA synthesis. nsp7 and nsp8 are important cofactors of the RTC, as they interact and regulate the activity of RNA- ... ...

Abstract	Coronavirus (CoV) non-structural proteins (nsps) assemble to form the replication-transcription complex (RTC) responsible for viral RNA synthesis. nsp7 and nsp8 are important cofactors of the RTC, as they interact and regulate the activity of RNA-dependent RNA polymerase (RdRp) and other nsps. To date, no structure of full-length SARS-CoV-2 nsp7:nsp8 complex has been published. Current understanding of this complex is based on structures from truncated constructs or with missing electron densities and complexes from related CoV species with which SARS-CoV-2 nsp7 and nsp8 share upwards of 90% sequence identity. Despite available structures being solved using crystallography and cryo-EM representing detailed snapshots of the nsp7:nsp8 complex, it is evident that the complex has a high degree of structural plasticity. However, relatively little is known about the conformational dynamics of the complex and how it assembles to interact with other nsps. Here, the solution-based structural proteomic techniques, hydrogen-deuterium exchange mass spectrometry (HDX-MS) and crosslinking mass spectrometry (XL-MS), illuminate the structural dynamics of the SARS-CoV-2 full-length nsp7:nsp8 complex. The results presented from the two techniques are complementary and validate the interaction surfaces identified from the published three-dimensional heterotetrameric crystal structure of SARS-CoV-2 truncated nsp7:nsp8 complex. Furthermore, mapping of XL-MS data onto higher order complexes suggests that SARS-CoV-2 nsp7 and nsp8 do not assemble into a hexadecameric structure as implied by the SARS-CoV full-length nsp7:nsp8 crystal structure. Instead our results suggest that the nsp7:nsp8 heterotetramer can dissociate into a stable dimeric unit that might bind to nsp12 in the RTC without altering nsp7-nsp8 interactions.
Language	English
Publishing date	2021-03-06
Publishing country	United States
Document type	Preprint
DOI	10.1101/2021.03.06.434214
Database	MEDical Literature Analysis and Retrieval System OnLINE

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾

Article: Discovery of an NAD

Zhang, Xiao-Nan / Lam, Albert T / Cheng, Qinqin / Courouble, Valentine V / Strutzenberg, Timothy S / Li, Jiawei / Wang, Yiling / Pei, Hua / Stiles, Bangyan L / Louie, Stan G / Griffin, Patrick R / Zhang, Yong

Chemical science

2022 Volume 13, Issue 7, Page(s) 1982–1991

Abstract: Among various protein posttranslational modifiers, poly-ADP-ribose polymerase 1 (PARP1) is a key player for regulating numerous cellular processes and events through enzymatic attachments of target proteins with ADP-ribose units donated by nicotinamide ... ...

Abstract	Among various protein posttranslational modifiers, poly-ADP-ribose polymerase 1 (PARP1) is a key player for regulating numerous cellular processes and events through enzymatic attachments of target proteins with ADP-ribose units donated by nicotinamide adenine dinucleotide (NAD
Language	English
Publishing date	2022-01-27
Publishing country	England
Document type	Journal Article
ZDB-ID	2559110-1
ISSN	2041-6539 ; 2041-6520
ISSN (online)	2041-6539
ISSN	2041-6520
DOI	10.1039/d1sc06256e
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Article ; Online: Revealing the Structural Plasticity of SARS-CoV-2 nsp7 and nsp8 Using Structural Proteomics.

Courouble, Valentine V / Dey, Sanjay Kumar / Yadav, Ruchi / Timm, Jennifer / Harrison, Jerry Joe E K / Ruiz, Francesc X / Arnold, Eddy / Griffin, Patrick R

Journal of the American Society for Mass Spectrometry

2021 Volume 32, Issue 7, Page(s) 1618–1630

Abstract: Coronavirus (CoV) nonstructural proteins (nsps) assemble to form the replication-transcription complex (RTC) responsible for viral RNA synthesis. nsp7 and nsp8 are important cofactors of the RTC, as they interact and regulate the activity of RNA- ... ...

Abstract	Coronavirus (CoV) nonstructural proteins (nsps) assemble to form the replication-transcription complex (RTC) responsible for viral RNA synthesis. nsp7 and nsp8 are important cofactors of the RTC, as they interact and regulate the activity of RNA-dependent RNA polymerase and other nsps. To date, no structure of the full-length SARS-CoV-2 nsp7:nsp8 complex has been published. The current understanding of this complex is based on structures from truncated constructs, with missing electron densities, or from related CoV species where SARS-CoV-2 nsp7 and nsp8 share upward of 90% sequence identity. Despite available structures solved using crystallography and cryo-EM representing detailed static snapshots of the nsp7:nsp8 complex, it is evident that the complex has a high degree of structural plasticity. However, relatively little is known about the conformational dynamics of the individual proteins and how they complex to interact with other nsps. Here, the solution-based structural proteomic techniques, hydrogen-deuterium exchange mass spectrometry (HDX-MS) and cross-linking mass spectrometry (XL-MS), illuminate the dynamics of SARS-CoV-2 full-length nsp7 and nsp8 proteins and the nsp7:nsp8 protein complex. Results presented from the two techniques are complementary and validate the interaction surfaces identified from the published three-dimensional heterotetrameric crystal structure of the SARS-CoV-2 truncated nsp7:nsp8 complex. Furthermore, mapping of XL-MS data onto higher-order complexes suggests that SARS-CoV-2 nsp7 and nsp8 do not assemble into a hexadecameric structure as implied by the SARS-CoV full-length nsp7:nsp8 crystal structure. Instead, our results suggest that the nsp7:nsp8 heterotetramer can dissociate into a stable dimeric unit that might bind to nsp12 in the RTC without significantly altering nsp7-nsp8 interactions.
MeSH term(s)	COVID-19/virology ; Coronavirus RNA-Dependent RNA Polymerase/chemistry ; Coronavirus RNA-Dependent RNA Polymerase/genetics ; Coronavirus RNA-Dependent RNA Polymerase/metabolism ; Humans ; Hydrogen Deuterium Exchange-Mass Spectrometry ; Models, Molecular ; Protein Conformation ; Proteomics/methods ; SARS-CoV-2/chemistry ; Viral Nonstructural Proteins/chemistry ; Viral Nonstructural Proteins/genetics ; Viral Nonstructural Proteins/metabolism
Chemical Substances	NS8 protein, SARS-CoV-2 ; Viral Nonstructural Proteins ; Coronavirus RNA-Dependent RNA Polymerase (EC 2.7.7.48) ; NSP7 protein, SARS-CoV-2 (EC 2.7.7.48)
Language	English
Publishing date	2021-06-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	1073671-2
ISSN	1879-1123 ; 1044-0305
ISSN (online)	1879-1123
ISSN	1044-0305
DOI	10.1021/jasms.1c00086
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 4618: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 241: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Biochemical and structural insights into SARS-CoV-2 polyprotein processing by Mpro.

Yadav, Ruchi / Courouble, Valentine V / Dey, Sanjay K / Harrison, Jerry Joe E K / Timm, Jennifer / Hopkins, Jesse B / Slack, Ryan L / Sarafianos, Stefan G / Ruiz, Francesc X / Griffin, Patrick R / Arnold, Eddy

Science advances

2022 Volume 8, Issue 49, Page(s) eadd2191

Abstract: SARS-CoV-2, a human coronavirus, is the causative agent of the COVID-19 pandemic. Its genome is translated into two large polyproteins subsequently cleaved by viral papain-like protease and main protease (Mpro). Polyprotein processing is essential yet ... ...

Abstract	SARS-CoV-2, a human coronavirus, is the causative agent of the COVID-19 pandemic. Its genome is translated into two large polyproteins subsequently cleaved by viral papain-like protease and main protease (Mpro). Polyprotein processing is essential yet incompletely understood. We studied Mpro-mediated processing of the nsp7-11 polyprotein, whose mature products include cofactors of the viral replicase, and identified the order of cleavages. Integrative modeling based on mass spectrometry (including hydrogen-deuterium exchange and cross-linking) and x-ray scattering yielded a nsp7-11 structural ensemble, demonstrating shared secondary structural elements with individual nsps. The pattern of cross-links and HDX footprint of the C145A Mpro and nsp7-11 complex demonstrate preferential binding of the enzyme active site to the polyprotein junction sites and additional transient contacts to help orient the enzyme on its substrate for cleavage. Last, proteolysis assays were used to characterize the effect of inhibitors/binders on Mpro processing/inhibition using the nsp7-11 polyprotein as substrate.
Language	English
Publishing date	2022-12-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.add2191
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Patient-derived Siglec-6-targeting antibodies engineered for T-cell recruitment have potential therapeutic utility in chronic lymphocytic leukemia.

Cyr, Matthew G / Mhibik, Maissa / Qi, Junpeng / Peng, Haiyong / Chang, Jing / Gaglione, Erika M / Eik, David / Herrick, John / Venables, Thomas / Novick, Scott J / Courouble, Valentine V / Griffin, Patrick R / Wiestner, Adrian / Rader, Christoph

Journal for immunotherapy of cancer

2022 Volume 10, Issue 11

Abstract: Background: Despite numerous therapeutic options, safe and curative therapy is unavailable for most patients with chronic lymphocytic leukemia (CLL). A drawback of current therapies such as the anti-CD20 monoclonal antibody (mAb) rituximab is the ... ...

Abstract	Background: Despite numerous therapeutic options, safe and curative therapy is unavailable for most patients with chronic lymphocytic leukemia (CLL). A drawback of current therapies such as the anti-CD20 monoclonal antibody (mAb) rituximab is the elimination of all healthy B cells, resulting in impaired humoral immunity. We previously reported the identification of a patient-derived, CLL-binding mAb, JML-1, and identified sialic acid-binding immunoglobulin-like lectin-6 (Siglec-6) as the target of JML-1. Although little is known about Siglec-6, it appears to be an attractive target for cancer immunotherapy due to its absence on most healthy cells and tissues. Methods: We used a target-specific approach to mine for additional patient-derived anti-Siglec-6 mAbs. To assess the therapeutic utility of targeting Siglec-6 in the context of CLL, T cell-recruiting bispecific antibodies (T-biAbs) that bind to Siglec-6 and CD3 were engineered into single-chain variable fragment-Fc and dual-affinity retargeting (DART)-Fc constructs. T-biAbs were evaluated for their activity in vitro, ex vivo, and in vivo. Results: We discovered the anti-Siglec-6 mAbs RC-1 and RC-2, which bind with higher affinity than JML-1 yet maintain similar specificity. Both JML-1 and RC-1 T-biAbs were effective at activating T cells and killing Siglec-6 Conclusion: Siglec-6-targeting T-biAbs are highly potent and specific for eliminating Siglec-6 Trial registration number: NCT00923507.
MeSH term(s)	Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy ; T-Lymphocytes ; B-Lymphocytes ; Antibodies, Monoclonal/pharmacology ; Antibodies, Monoclonal/therapeutic use ; Immunotherapy
Chemical Substances	Antibodies, Monoclonal
Language	English
Publishing date	2022-11-28
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, N.I.H., Extramural
ZDB-ID	2719863-7
ISSN	2051-1426 ; 2051-1426
ISSN (online)	2051-1426
ISSN	2051-1426
DOI	10.1136/jitc-2022-004850
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Differential Modulation of Nuclear Receptor LRH-1 through Targeting Buried and Surface Regions of the Binding Pocket.

Cato, Michael L / Cornelison, Jeffery L / Spurlin, Racheal M / Courouble, Valentine V / Patel, Anamika B / Flynn, Autumn R / Johnson, Alyssa M / Okafor, C Denise / Frank, Filipp / D'Agostino, Emma H / Griffin, Patrick R / Jui, Nathan T / Ortlund, Eric A

Journal of medicinal chemistry

2022 Volume 65, Issue 9, Page(s) 6888–6902

Abstract: Liver receptor homologue-1 (LRH-1) is a phospholipid-sensing nuclear receptor that has shown promise as a target for alleviating intestinal inflammation and metabolic dysregulation in the liver. LRH-1 contains a large ligand-binding pocket, but ... ...

Abstract	Liver receptor homologue-1 (LRH-1) is a phospholipid-sensing nuclear receptor that has shown promise as a target for alleviating intestinal inflammation and metabolic dysregulation in the liver. LRH-1 contains a large ligand-binding pocket, but generating synthetic modulators has been challenging. We have had recent success generating potent and efficacious agonists through two distinct strategies. We targeted residues deep within the pocket to enhance compound binding and residues at the mouth of the pocket to mimic interactions made by phospholipids. Here, we unite these two designs into one molecule to synthesize the most potent LRH-1 agonist to date. Through a combination of global transcriptomic, biochemical, and structural studies, we show that selective modulation can be driven through contacting deep versus surface polar regions in the pocket. While deep pocket contacts convey high affinity, contacts with the pocket mouth dominate allostery and provide a phospholipid-like transcriptional response in cultured cells.
MeSH term(s)	Cell Line ; Phospholipids/metabolism ; Receptors, Cytoplasmic and Nuclear
Chemical Substances	Phospholipids ; Receptors, Cytoplasmic and Nuclear
Language	English
Publishing date	2022-05-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	218133-2
ISSN	1520-4804 ; 0022-2623
ISSN (online)	1520-4804
ISSN	0022-2623
DOI	10.1021/acs.jmedchem.2c00235
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.B 151: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MB 1: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: A Bifunctional NAD

Lam, Albert T / Zhang, Xiao-Nan / Courouble, Valentine V / Strutzenberg, Timothy S / Pei, Hua / Stiles, Bangyan L / Louie, Stan G / Griffin, Patrick R / Zhang, Yong

ACS chemical biology

2021 Volume 16, Issue 2, Page(s) 389–396

Abstract: Protein poly-ADP-ribosylation (PARylation) is a heterogeneous and dynamic post-translational modification regulated by various writers, readers, and erasers. It participates in a variety of biological events and is involved in many human diseases. ... ...

Abstract	Protein poly-ADP-ribosylation (PARylation) is a heterogeneous and dynamic post-translational modification regulated by various writers, readers, and erasers. It participates in a variety of biological events and is involved in many human diseases. Currently, tools and technologies have yet to be developed for unambiguously defining readers and erasers of individual PARylated proteins or cognate PARylated proteins for known readers and erasers. Here, we report the generation of a bifunctional nicotinamide adenine dinucleotide (NAD
MeSH term(s)	Azides/chemical synthesis ; Azides/metabolism ; Azides/radiation effects ; Click Chemistry ; Cross-Linking Reagents/chemical synthesis ; Cross-Linking Reagents/metabolism ; Cross-Linking Reagents/radiation effects ; Diazomethane/analogs & derivatives ; Diazomethane/metabolism ; Diazomethane/radiation effects ; HEK293 Cells ; Humans ; NAD/chemical synthesis ; NAD/metabolism ; NAD/radiation effects ; Poly (ADP-Ribose) Polymerase-1/metabolism ; Poly ADP Ribosylation ; Protein Processing, Post-Translational ; Proteome/chemistry ; Proteome/metabolism ; Proteomics ; Ultraviolet Rays
Chemical Substances	Azides ; Cross-Linking Reagents ; Proteome ; NAD (0U46U6E8UK) ; Diazomethane (60A625P70P) ; PARP1 protein, human (EC 2.4.2.30) ; Poly (ADP-Ribose) Polymerase-1 (EC 2.4.2.30)
Language	English
Publishing date	2021-02-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1554-8937
ISSN (online)	1554-8937
DOI	10.1021/acschembio.0c00937
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Biochemical and structural insights into SARS-CoV-2 polyprotein processing by Mpro

Yadav, Ruchi / Courouble, Valentine V. / Dey, Sanjay K. / Harrison, Jerry Joe E.K. / Timm, Jennifer / Hopkins, Jesse B. / Slack, Ryan L. / Sarafianos, Stefan G. / Ruiz, Francesc X. / Griffin, Patrick R. / Arnold, Eddy

bioRxiv

Abstract: SARS-CoV-2, a human coronavirus, is the causative agent of the COVID-19 pandemic. Its ~30 kb RNA genome is translated into two large polyproteins subsequently cleaved by viral papain-like protease and main protease (Mpro/nsp5). Polyprotein processing is ... ...

Abstract	SARS-CoV-2, a human coronavirus, is the causative agent of the COVID-19 pandemic. Its ~30 kb RNA genome is translated into two large polyproteins subsequently cleaved by viral papain-like protease and main protease (Mpro/nsp5). Polyprotein processing is essential yet incompletely understood. We studied Mpro-mediated processing of the nsp7-10/11 polyprotein, whose mature products are cofactors of the viral replicase, identifying the order of cleavages as: 1) nsp9-10, 2) nsp8-9/nsp10-11, and 3) nsp7-8. Integrative modeling based on mass spectrometry (including hydrogen-deuterium exchange and cross-linking) and X-ray scattering yielded three-dimensional models of the nsp7-10/11 polyprotein. Our data suggest that the nsp7-10/11 structure in complex with Mpro strongly resembles the unbound polyprotein, and that both polyprotein conformation and junction accessibility determine the preference and order of cleavages. Finally, we used limited proteolysis assays to characterize the effect of a series of inhibitors/binders on Mpro processing of nsp7-11 and Mpro inhibition using a polyprotein substrate.
Keywords	covid19
Language	English
Publishing date	2022-05-30
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2022.05.27.493767
Database	COVID19

Full text online

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Prion-like low complexity regions enable avid virus-host interactions during HIV-1 infection.

Wei, Guochao / Iqbal, Naseer / Courouble, Valentine V / Francis, Ashwanth C / Singh, Parmit K / Hudait, Arpa / Annamalai, Arun S / Bester, Stephanie / Huang, Szu-Wei / Shkriabai, Nikoloz / Briganti, Lorenzo / Haney, Reed / KewalRamani, Vineet N / Voth, Gregory A / Engelman, Alan N / Melikyan, Gregory B / Griffin, Patrick R / Asturias, Francisco / Kvaratskhelia, Mamuka

Nature communications

2022 Volume 13, Issue 1, Page(s) 5879

Abstract: Cellular proteins CPSF6, NUP153 and SEC24C play crucial roles in HIV-1 infection. While weak interactions of short phenylalanine-glycine (FG) containing peptides with isolated capsid hexamers have been characterized, how these cellular factors ... ...

Abstract	Cellular proteins CPSF6, NUP153 and SEC24C play crucial roles in HIV-1 infection. While weak interactions of short phenylalanine-glycine (FG) containing peptides with isolated capsid hexamers have been characterized, how these cellular factors functionally engage with biologically relevant mature HIV-1 capsid lattices is unknown. Here we show that prion-like low complexity regions (LCRs) enable avid CPSF6, NUP153 and SEC24C binding to capsid lattices. Structural studies revealed that multivalent CPSF6 assembly is mediated by LCR-LCR interactions, which are templated by binding of CPSF6 FG peptides to a subset of hydrophobic capsid pockets positioned along adjoining hexamers. In infected cells, avid CPSF6 LCR-mediated binding to HIV-1 cores is essential for functional virus-host interactions. The investigational drug lenacapavir accesses unoccupied hydrophobic pockets in the complex to potently impair HIV-1 inside the nucleus without displacing the tightly bound cellular cofactor from virus cores. These results establish previously undescribed mechanisms of virus-host interactions and antiviral action.
MeSH term(s)	Humans ; Anti-HIV Agents ; Capsid Proteins/metabolism ; Drugs, Investigational ; Glycine/metabolism ; HIV Infections ; HIV-1/metabolism ; Host Microbial Interactions ; mRNA Cleavage and Polyadenylation Factors/metabolism ; Nuclear Pore Complex Proteins/metabolism ; Phenylalanine/metabolism ; Prions/metabolism ; Virus Integration
Chemical Substances	Anti-HIV Agents ; Capsid Proteins ; Drugs, Investigational ; Glycine (TE7660XO1C) ; mRNA Cleavage and Polyadenylation Factors ; Nuclear Pore Complex Proteins ; NUP153 protein, human ; Phenylalanine (47E5O17Y3R) ; Prions
Language	English
Publishing date	2022-10-06
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-33662-6
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Resolving the Dynamic Motions of SARS-CoV-2 nsp7 and nsp8 Proteins Using Structural Proteomics

Courouble, Valentine / Dey, Sanjay / Yadav, Ruchi / Timm, Jennifer / Harrison, Jerry / Ruiz, Francesc X / Arnold, Eddy / Griffin, Patrick R

bioRxiv

Abstract	Coronavirus (CoV) non-structural proteins (nsps) assemble to form the replication-transcription complex (RTC) responsible for viral RNA synthesis. nsp7 and nsp8 are important cofactors of the RTC, as they interact and regulate the activity of RNA-dependent RNA polymerase (RdRp) and other nsps. To date, no structure of full-length SARS-CoV-2 nsp7:nsp8 complex has been published. Current understanding of this complex is based on structures from truncated constructs or with missing electron densities and complexes from related CoV species with which SARS-CoV-2 nsp7 and nsp8 share upwards of 90% sequence identity. Despite available structures being solved using crystallography and cryo-EM representing detailed snapshots of the nsp7:nsp8 complex, it is evident that the complex has a high degree of structural plasticity. However, relatively little is known about the conformational dynamics of the complex and how it assembles to interact with other nsps. Here, the solution-based structural proteomic techniques, hydrogen-deuterium exchange mass spectrometry (HDX-MS) and crosslinking mass spectrometry (XL-MS), illuminate the structural dynamics of the SARS-CoV-2 full-length nsp7:nsp8 complex. The results presented from the two techniques are complementary and validate the interaction surfaces identified from the published three-dimensional heterotetrameric crystal structure of SARS-CoV-2 truncated nsp7:nsp8 complex. Furthermore, mapping of XL-MS data onto higher order complexes suggests that SARS-CoV-2 nsp7 and nsp8 do not assemble into a hexadecameric structure as implied by the SARS-CoV full-length nsp7:nsp8 crystal structure. Instead our results suggest that the nsp7:nsp8 heterotetramer can dissociate into a stable dimeric unit that might bind to nsp12 in the RTC without altering nsp7-nsp8 interactions.
Keywords	covid19
Language	English
Publishing date	2021-03-06
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2021.03.06.434214
Database	COVID19

Full text online

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

To top

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

Full text online

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Full text online

Kategorien

Inter-library loan at ZB MED